Effects of Analgesics and Related Compounds on Renal Metabolism in Rats

Abstract

Metabolic effects of p-aminophenol were compared with those of paracetamol and other analgesics in studies of rat liver and kidney in vitro. p-Aminophenol injected into rats inhibited gluconeogenesis from lactate in renal cortical tubules but not in isolated hepatocytes, and reduced kidney ATP content without affecting the ATP content of liver. Perfused kidneys from rats previously injected with p-aminophenol showed 50% reduction of ATP content, severe inhibition of Na+ reabsorption and reduction of inulin clearance without significant inhibition of gluconeogenesis from lactate. Paracetamol, p-phenetidine, phenazone and aspirin, when given i.v. to rats, had no effect on renal tubular glucose synthesis from lactate or pyruvate. Paracetamol and aspirin slightly inhibited renal glucose synthesis from several different substrates when added directly to tubules. Paracetamol (4 mmol/1) inhibited glucose synthesis from lactate and other substrates by 50% or more in isolated hepatocytes. Glucose synthesis from lactate was inhibited 30% by concentrations of paracetamol as low as 0.5 mmol/1. p-Aminophenol apparently is a potent inhibitor of proximal tubular function with its main site of action the inhibition of ATP synthesis and energy production. The primary hepatotoxic effect of paracetamol is confirmed. [Many patients abusing compound analgesics develop chronic renal disease.].